Endocrine consequences of prolonged ovarian hyperstimulation: hyperprolactinemia, follicular atresia, and premature luteinization.

Eighteen normal ovulatory cynomolgus (Macaca fascicularis) monkeys were given an extended fixed-dose regimen of human menopausal gonadotropin (hMG), which was followed by human chorionic gonadotropin (hCG) administration. Ovarian hyperstimulation developed in responsive subjects to various degrees. Based on their serum estradiol (E2) response, 16 were arbitrarily categorized as high responders (E2 greater than 1000 pg/ml), 3 were medium responders (E2 500 to 1000 pg/ml), and 2 were low responders (E2 150 to 500 pg/ml). Interestingly, one female did not respond to exogenous gonadotropin therapy. The endocrine consequences of prolonged ovarian hyperstimulation include (1) hyperprolactinemia in the luteal phase of 50% of responsive monkeys; (2) frequent atresia of growing follicles, marked by a precipitous decline in serum E2, despite continuous hMG therapy; and (3) seven monkeys with premature serum progesterone elevations up to 1 week before hCG injection, without an overt luteinizing hormone surge. Only 1 of 18 females manifested a typical midcycle luteinizing hormone surge during hMG/hCG treatment. These findings have physiologic implications that are relevant to ovulation induction and in vitro fertilization therapy in infertile women.